Risk Of Developing Bladder Cancer Research Articles

Exploring the DNA Methylation Profile of Genes Associated with Bladder Cancer in Bladder Tissue of Patients with Neurogenic Lower Urinary Tract Dysfunction.

DNA methylation is an epigenetic process that commonly occurs in genes' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes' promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARβ, DAPK, hTERT, and APC genes' promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-β was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs (p = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients.

Detection of cytological abnormalities in urothelial cells from individuals previously exposed or currently infected with Schistosoma haematobium.

Urinary schistosomiasis has long been associated with bladder cancer, but it is still not clear the mechanisms involved. Schistosoma haematobium causes injury and disruptions in the integrity of the urothelium. The cellular and immunologic responses to the infection lead to the formation of granulomata. The ability to use cellular morphological changes to predict the risk of developing bladder cancer following S. haematobium infection is thus important. This study assessed the cellular changes in the urine associated with schistosomiasis and the potential of routine urine being used as a risk predictor of the development of bladder cancer. Urine samples (160) were screened for the presence of S. haematobium ova. Smears stained with the Papanicolaou method were evaluated using light microscopy to determine the cell populations. A high prevalence (39.9%) of urinary schistosomiasis and haematuria (46.9%) was found among the participants. Polymorphonuclear cells, normal and reactive urothelial cells and lymphocytes were characteristic of S. haematobium infection. Squamous metaplastic cells (SMCs) were found in 48% and 47.1% of participants who have had past or current S. haematobium infection respectively, but were not found in participants who had no exposure to S. haematobium. These squamous metaplastic cells are in transition and are prone to malignant transformation when exposed to a carcinogenic agent. There is still a high burden of schistosomiasis in endemic communities in Ghana. by examining urine, one can find metaplastic cells and? dysplastic cells and thus predict cancer in SH-infested patients. Thus, routine urine cytology as a tool to monitor the risk of bladder cancer development is recommended.

Bladder cancer, inflammageing and microbiomes.

Ageing is correlated with elevated bladder cancer incidence, morbidity and mortality. Advanced age is also associated with elevated markers of chronic inflammation and perturbations in gut and urinary tract microbiota. One reason for the increased incidence and mortality of bladder cancer in the elderly might be that age-associated changes in multiple microbiomes induce systemic metabolic changes that contribute to immune dysregulation with potentially tumorigenic effects. The gut and urinary microbiomes could be dysregulated in bladder cancer, although the effect of these changes is poorly understood. Each of these domains - the immune system, gut microbiome and urinary microbiome - might also influence the response of patients with bladder cancer to treatment. Improved understanding of age-related alterations to the immune system and gut and urinary microbiomes could provide possible insight into the risk of bladder cancer development and progression in the elderly. In patients with bladder cancer, improved understanding of microbiota might also provide potential targets for therapeutic intervention.

Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort.

Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case-control study was to evaluate the implication of a selected SNP panel in the risk of BCa development in a Tunisian cohort. We were also interested in studying the interaction between this predictive panel and environmental risk factors. The case/control cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) was composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology). We have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR 2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non-smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A > G), ARNT/ rs1889740 (C > T) or GSTA4/rs17614751 (G-A) were respectively at 2.775, 3.069 and 6.608-fold increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa classes. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype. The determined association between environmental factors, genetic variations and the risk of Bca development may provide additional information to urologists that may help them for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies.

Scented Candles as an Unrecognized Factor that Increases the Risk of Bladder Cancer; Is There Enough Evidence to Raise a Red Flag?

The causes of bladder cancer are not yet fully uncovered, however the research has identified a number of factors that may increase the risk of developing this cancer. The chemical carcinogenesis of bladder cancer due to chronic exposure to aromatic hydrocarbons has been well-established. The identification of this correlation led to an improvement of safety measures in chemical industry and a gradual decrease of bladder cancer cases among workers. Nevertheless, in the majority of bladder cancer cases, the specific cause of the disease still can't be specified. It makes the question of unrecognized factors associated with bladder cancer development even more relevant. Taking under consideration known chemical carcinogenesis of bladder cancer, this minireview takes under investigation the possible link between using scented candles and a risk of bladder cancer development. Burning scented candles contain many of the substances that are associated with a bladder cancer. Furthermore the scented candles are not only very popular but also widely available on the market, with limited quality regulations and unspecified raw materials determining a spectrum of potentially dangerous substances emitted during burning.

Association of TP53 Arg72Pro polymorphism (rs1042522) with bladder cancer risk in the Ukrainian population

Aim. To determine the frequency of TP53 polymorphic variants in bladder cancer patients and define possible association of this polymorphism with a bladder cancer in Ukrainians patients. Methods. The genotypes of TP53 gene at codon 72 were detected by PCR with allele specific primers. We investigated Arg72Pro polymorphism in 114 DNA samples of patients with bladder cancer. The PCR-amplified DNA products were subjected to electrophoresis in 3 % agarose. Results. The distribution of genotypes in group of patients with a bladder cancer was: Arg/Arg – 59.6 % (n=68), Arg/Pro – 40.4 % (n=46), Pro/Pro – 0 % (n=0). Genotype frequencies in patients (χ2=7.28, p=0.0007) weren’t in agreement with Hardy-Weinberg equilibrium. There were significant differences in the frequency of genotypes between the healthy individuals and the cancer group patients. Our result showed that patients with bladder cancer had a significantly higher frequency of Arg/Arg (F=42.7, p<0.05) and a lower frequency of Pro/Arg (F=40.9, p<0.05) compared to controls. Conclusions. Our study allows us to suggest that Arg/Arg polymorphic variant of TP53 is associated with the higher risk of bladder cancer development in the Ukrainian population (OR = 5,6, 95 % CI = 3.19 to 9.34, p < 0.0001). Keywords: TP53 gene, bladder cancer, polymorphism Arg72Pro, Ukrainian population.

Association of Enhancer of Zeste 2 (EZH2) Genotypes with Bladder Cancer Risk in Taiwan.

Bladder cancer is the sixth most common cancer worldwide and its incidence is particularly high in many developed regions including southwestern Taiwan. However, the genetic contribution to the etiology of bladder cancer is not well-understood. The aim of this study was to evaluate the association of the enhancer of zeste homolog 2 (EZH2) genotypes with Taiwan bladder cancer risk. Three polymorphic variants of EZH2 were analyzed regarding their association with bladder cancer risk, and three hundred and seventy-five patients with bladder cancer and same number of age- and gender-matched healthy controls recruited were genotyped by the PCR-RFLP method. Among the three polymorphic sites examined, the genotypes of EZH2 rs887569 (C to T), but not rs41277434 (A to C) or rs3757441 (T to C), were positively associated with bladder cancer risk (p for trend =0.0146). Individuals with the EZH2 rs887569 TT genotypes were associated with decreased cancer risk than those with wild-type CC genotype. The stratified analyses showed that EZH2 rs887569 TT genotypes had protective effects on non-smokers but obviously not on smokers. Our findings provide evidence that the T allele of EZH2 rs887569 may be associated with the lower risk of bladder cancer development, especially among non-smokers.

MP36-02 POLYMORPHISMS OF MEMBRANE TRANSPORTING GENE SLCO1B3 AND DETOXIFICATION ENZYME NAT2 ASSOCIATE WITH BLADDER CANCER SUSCEPTIBILITY IN SMOKERS

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2015MP36-02 POLYMORPHISMS OF MEMBRANE TRANSPORTING GENE SLCO1B3 AND DETOXIFICATION ENZYME NAT2 ASSOCIATE WITH BLADDER CANCER SUSCEPTIBILITY IN SMOKERS Naohiro Fujimoto, Hoai Bui, Tatsuhiko Kubo, Hisato Inatomi, and Ryoichi Hamasuna Naohiro FujimotoNaohiro Fujimoto More articles by this author , Hoai BuiHoai Bui More articles by this author , Tatsuhiko KuboTatsuhiko Kubo More articles by this author , Hisato InatomiHisato Inatomi More articles by this author , and Ryoichi HamasunaRyoichi Hamasuna More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.730AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Varying combinations of genetic and environmental factors cause cancers including bladder cancer. Cigarette smoke contains lots of chemicals including over 60 well-established carcinogens and smoking is responsible for bladder cancer development. Cellular uptake and detoxification of carcinogens may play a role in cancer development. Organic anion-transporting polypeptides (OATPs) encoded by SLCOs mediate cellular uptake of a broad range of substrates including possible carcinogens. SLCOs are polymorphic, and single nucleotide polymorphisms (SNPs) of those genes alter transporting efficiency of substrates. We investigated the association between SNPs of SLCOs in combination with SNPs of NAT2 (detoxification enzyme) and bladder cancer risk in smokers in Japanese population. METHODS We analysed SNPs at rs2306283, rs4149117 and rs12422149 in SLCO1B1, SLCO1B3 and SLCO2B1, respectively, in 237 bladder cancer patients and 248 non-bladder cancer patients. Smoking status was grouped as smoker or never-smoker. SNPs were analyzed by DNA sequencing of peripheral blood cells. Combination effect of SLCO and NAT2 genotypes was also analyzed. NAT2 genotypes were divided into the rapid (wild type allele homo/heterozygotes: WT/WT, WT/M1-3) and the slow acetylator genotypes (two mutant alleles: M1-3/M1-3) RESULTS The number of smokers was 243 (143 in bladder cancer and 100 in non-bladder cancer patients).and bladder cancer was significantly frequent in smoker group (p<0,001). In non-smokers, polymorphisms of SLCOs were not associated with bladder cancer risk. In smokers, frequencies of SLCO1B3 G alleles and T alleles were 66.1% and 33.9% in bladder cancer patients, respectively, and 77.8% and 22.2% in non-bladder cancer patients, respectively. SLCO1B3 TT and TT/TG genotypes were at significantly higher risk of bladder cancer than GG genotype (TT vs GG: OR=4.75, p=0.011, TT/TG vs GG: OR=1.90, p=0.015). Genotypes of SLCO1B1 and SLCO2B1 were not associated with bladder cancer risk in smokers. In combination analyses of SLCO1B3 and NAT2 genotypes in smokers, the patients having SLCO1B3 TT/TG and NAT2 slow types were at significantly higher risk of bladder cancer than those with SLCO1B3 GG and NAT2 rapid genotypes (OR=3.95, p=0.014). CONCLUSIONS Our results, for the first time, demonstrated that genetic variants of SLCO1B3 rs4149117 were associated with bladder cancer risk and genetic variants of NAT2 further increased the risk. SLCO1B3 may be a potential biomarker for assessing the risk of bladder cancer development in smokers © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e428 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naohiro Fujimoto More articles by this author Hoai Bui More articles by this author Tatsuhiko Kubo More articles by this author Hisato Inatomi More articles by this author Ryoichi Hamasuna More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

ObjectiveWe investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients.Patients and MethodsA hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR) with corresponding 95% confidence interval (95%CI) was calculated.ResultsThe glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1–4.2, p = 0.032). The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4–34.7, p = 0.001). The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1–19.7, p = 0.001). The risk of bladder cancer development was 5.3–fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9–15.1, p = 0.002). Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9–22.5, p = 0.067).ConclusionNull or low-activity genotypes of the glutathione S-transferase A1, T1, and P1 did not contribute independently towards the risk of bladder cancer in males. However, in association with occupational exposure, low activity glutathione S-transferase A1 and glutathione S-transferase M1-null as well as glutathione S-transferase T1-active genotypes increase individual susceptibility to bladder cancer.

No evidence of correlation between p53 codon 72 polymorphism and risk of bladder cancer in Moroccan patients

Background: The p53 codon 72 polymorphism has been investigated extensively for its association with various cancers around the world. Several studies have investigated the association between p53 polymorphism at codon 72 and risk of developing bladder cancer, but the results are still controversial. Aim: The aim of our study was to evaluate the association between the p53 polymorphism and the bladder cancer risk among Moroccan patients. Materials and Methods: This study was carried out on fresh biopsies from 41 patients with bladder cancer confirmed and 38 blood samples from control donors. Deoxyribonucleic acid was genotyped by Allele-specific polymerase chain reaction using specific primers to each polymorphic variant. Results: Frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes among cases were 17%, 66%, and 17%, while in controls the frequencies of Arg/Arg, Arg/Pro and Pro/Pro were 15.8%, 63.2%, and 21%, respectively. The difference between cases and controls was not statistically significant. An increased risk of bladder cancer development was not clearly related to any polymorphic variant of the p53 Arg72Pro in our study group from Moroccan population. Moreover, the frequency of the Arg allele was higher (71.45%) than the Pro allele (28.55%) in high stage of bladder tumors, but this difference was statistically not significant. Conclusion: This study suggests that Arg allele could be more involved in developing bladder tumor in Moroccan population than the Pro allele. Therefore, enlarging the sampling will be necessary to confirm this association in Moroccan population.

BASIC SCIENCE Polymorphic variants of H-RAS protooncogene and their possible role in bladder cancer etiology

Introduction H-RAS gene is a protooncogene encoding p21ras, a small protein with GTPase activity. This protein is a component of many signaling cascades, while mutations in H-RAS gene are often found in urinary bladder cancer and leads to continuous transmission of signals stimulating cancer cell growth and proliferation. The T81C polymorphism of H-RAS gene is a SNP, which, although does not seem to impair p21ras protein structure and function, may contribute to the development of bladder cancer.ObjectivesThe aim of our study was to characterize the prevalence and clinical significance of T81C polymorphism in patients with diagnosed bladder cancer.Materials and methods132 patients with diagnosed urinary bladder cancer were included in this study. The control group consisted of 106 healthy individuals. The experimental material was DNA, isolated from tumor tissue and peripheral blood lymphocytes. T81C polymorphism was detected using the MSSCP method and DNA sequencing.ResultsIn the examined DNA samples, frequent polymorphic variations were found in codon 27 of H-RAS gene. In order to assess the clinical relevance of the polymorphism, the results were compared with those for the control group. The homozygous CC variant occurred more frequently in bladder cancer patients than in healthy individuals.ConclusionsDNA polymorphisms start to play an important role in evaluation of disease risk and progression. The occurrence of multiple variants of the same gene may contribute to differences in reactions to specific medications and sensitivity to carcinogens or DNA repair capacity. Our study demonstrated T81C polymorphism of H-RAS gene to have seemingly been associated with an increased risk of bladder cancer development.

The A148T variant of CDKN2A gene in bladder cancer

Results We found common polymorphic variants reported in the literature at codon 148 in exon 2 (Arg148Thr) and at nucleotides 500 and 540 in the 3’untranslated region which were not considered to be functional variants. We compared the obtained frequencies for the particular CDKN2A variants with the control group for the Polish population examined by Debniak and colleagues (Cancer Research 2005) and we found a significant difference in A148T polymorphism occurrence in the group of the bladder cancer patients (G test, table 2 ×2: NBLADDER CANCER =80, NCONTROL=1210, G=10.214, p g, Nt540c>t polymorphisms recorded in the group of the bladder cancer patients in our study is not different from those recorded in the control group. Conclusion The A148T variant of CDKN2A gene seems to be associated with an increased risk of bladder cancer development.

Personal Use of Hair Dyes and the Risk of Bladder Cancer: Results of a Meta-Analysis

This study examined the methodology of observational studies that explored an association between personal use of hair dye products and the risk of bladder cancer. Data were pooled from epidemiological studies using a general variance-based meta-analytic method that employed confidence intervals. The outcome of interest was a summary relative risk (RRs) reflecting the risk of bladder cancer development associated with use of hair dye products vs. non-use. Sensitivity analyses were performed to explain any observed statistical heterogeneity and to explore the influence of specific study characteristics of the summary estimate of effect. Initially combining homogenous data from six case-control and one cohort study yielded a non-significant RR of 1.01 (0.92, 1.11), suggesting no association between hair dye use and bladder cancer development. Sensitivity analyses examining the influence of hair dye type, color, and study design on this suspected association showed that uncontrolled confounding and design limitations contributed to a spurious non-significant summary RR. The sensitivity analyses yielded statistically significant RRs ranging from 1.22 (1.11, 1.51) to 1.50 (1.30, 1.98), indicating that personal use of hair dye products increases bladder cancer risk by 22% to 50% vs. non-use. The available epidemiological data suggest an association between personal use of hair dye products and increased risk of bladder cancer.

Fluid Intake and the Risk of Tumor Recurrence in Patients With Superficial Bladder Cancer

High fluid intake has been associated with a decreased risk of bladder cancer development in men. We evaluated whether higher fluid intake can impact tumor recurrence rates in patients with superficial bladder cancer. We conducted a prospective single institution analysis of fluid intake in 267 consecutive patients with superficial bladder cancer undergoing routine bladder cancer surveillance between January 1998 and December 2001. Fluid intake questionnaires, urine cytology and physical examination were routinely performed at each surveillance cystoscopy. Cytological and histological recurrences were recorded. All patients had a minimum followup of 2 years. No relationship between fluid intake and tumor recurrence was demonstrated. Average daily fluid intake was 2,654 ml daily, which was well within the highest protective level (more than 2,531 ml) previously reported. However, multivariate analysis failed to show a protective effect against recurrence at any level of fluid intake. Increasing age correlated with decreased fluid intake (Pearson's correlation coefficient -0.19, p = 0.0015), but did not increase the risk of recurrence (p = 0.59). Single fluid intake data correlated with the average of additional fluid intakes (median 5 per patient) in the same patient (Pearson's correlation coefficient, 0.45, p < 0.0001). Of the study population 123 patients (46%) experienced 1 or more tumor recurrences (range 0 to 11) within a median followup of 2.6 years. Our prospective study of fluid intake in patients with superficial bladder cancer at risk for recurrence did not find any association between daily fluid intake levels and tumor recurrence.

Glutathione S-transferase M1 gene polymorphism in bladder cancer patients: a marker for invasive bladder cancer?

The glutathione S-transferase M1 ( GSTM1) gene is polymorphic in humans, and the deficiency in enzyme activity of GSTM1 is caused by the inherited homozygous absence of the GSTM1 gene, or the “null” genotype ( GSTM1, 0/0). The increased risk of bladder cancer has been shown to correspond with this gene defect. No reports, however, have been found in the literature regarding GSTM1 gene deficiency with superficial and invasive bladder cancer. In this study, we examined the association of the GSTM1-null genotype with superficial and invasive bladder cancer. Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the GSTM1 gene defect in Turkish patients with superficial bladder cancer ( N = 61), invasive bladder cancer ( N = 42), and control subjects ( N = 202) who had no history of cancer. The GSTM1 null genotype was observed in 34.7% of the control subjects and in 54.3% of total bladder cancer patients (OR: 2.246; 95% CI: 1.384–3.645, P: 0.00094). In other words, the presence of the GSTM1-null genotype significantly increased the risk of bladder cancer development. Among invasive bladder cancers, the frequency of the GSTM1-null genotype was 64.3% (OR: 0.294, 95% CI: 0.147–0.590, P: 0.0003). This was also significantly higher than control subjects, indicating that patients carrying this genotype were at increased risk for developing invasive bladder cancer. This relationship was not statistically significant in the superficial bladder cancer group (OR: 0.585, 95% CI: 0.327–1.045, P: 0.06). Our results indicate that GSTM1 gene polymorphism should be considered as an important risk modifier in the development of bladder cancer and might be used as a predictive marker for invasive bladder cancer.

Detection of adenocarcinoma by urinary microsatellite analysis after augmentation cystoplasty

Augmentation cystoplasty is associated with an increased risk of bladder cancer development between 10 and 20 years after augmentation. Using microsatellite analysis, we analyzed urine obtained before surgical resection of the malignant lesion from a patient who developed invasive adenocarcinoma after augmentation cystoplasty. Loss of heterozygosity was identified in both urine and tumor samples from this patient. This observation suggests that microsatellite urine analysis may be useful as a monitoring tool for patients after augmentation cystoplasty.

Quantitative trait loci associated with promoting effects of sodium L-ascorbate on two-stage bladder carcinogenesis in rats.

In the two‐stage rat bladder carcinogenesis model using N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN) as an initiator and sodium l‐ascorbate (SA) as a promoter, we found a notable strain difference between F344/DuCrj (F344) and WS/Shi (WS) rats in susceptibility to the promoting effect of SA. Twenty each of F344, WS and reciprocal F1 hybrid rats were given 0.05% BBN in their drinking water for 4 weeks and then a basal diet with (BBN‐SA group) or without (BBN group) a 5% SA supplement for 32 weeks. In F344 and also in reciprocal F1 hybrids, the number of tumors per rat was significantly higher in the BBN‐SA group than in the BBN group (P<0.0001). In contrast, WS rats were not significantly affected by either treatment (P=0.8). These findings indicate that F344 rats are highly susceptible to the promoter effect of SA, but WS rats are not. Linkage analysis of 108 WS X (WSXF344) F1 backcrosses revealed that this difference was related to a quantitative trait locus mapped on rat Chr. 17 (maximum LOD score, 3.86) named Bladder Tumor Susceptible‐I and possibly another locus on Chr. 5 (maximum LOD score, 2.39). This study has provided the first evidence that host genes influence the risk of bladder cancer development.

THE ETIOLOGY OF BLADDER CANCER‐ARE THERE ANY NEW CLUES OR PREDICTORS OF BEHAVIOR?

It is well documented that the etiology of bladder cancer involves environmental factors. Most chemical carcinogens probably affect the urothelial cells via their presence in the urine. As an important cofactor, cell proliferative activity may be increased by urinary bladder infection, irritation by bladder stones or through the action of a variety of endogenously produced direct acting chemicals or agents. Among the known causative factors, avoidable major ones are occupational exposure to certain chemicals such as benzidine and 4-aminobiphenyl, cigarette smoking and bilharzial infection, which could be eradicated by a combination of praziquantel, antihelminth therapy, education and improvements in social welfare. An anticarcinogenic drug, cyclophosphamide, used as an immunosuppressive agent also seems to be associated with a high risk of idiopathic induction of bladder cancer and physicians should therefore pay particular attention to its diverse effects when considering its prescription. In contrast to the above, the consumption of coffee and tea including artificial sweeteners is now thought unlikely to be major risk. So far there is no good biochemical tool to predict individual exposure to bladder carcinogens/or relative risk of bladder cancer development. However, acetylation capacity can be applied to assess susceptibility to carcinogenic amines in people exposed in their working environment. Progress in molecular biological analysis will hopefully bring to light etiology-specific DNA damage in the bladder tumors and prove useful for prediction of tumor behavior in the near future.